Biomedical subjects

Attila Nagy

Publications and source records attributed to Attila Nagy.

58 records · Page 4Linked to original sources

PubMed2002

Effective treatment of experimental ES-2 human ovarian cancers with a cytotoxic analog of luteinizing hormone-releasing hormone AN-207.

The receptors for luteinizing hormone-releasing hormone (LHRH) are found in 80% of human ovarian carcinomas. These receptors can be used for targeted chemotherapy with cytotoxic analogs of LHRH, such as AN-207, consisting of 2-pyrrolinodoxorubicin (AN-201) linked to [D-Lys ]LHRH. We investigated the effects of AN-207 and AN-201 on the growth of LHRH receptor-positive ES-2 human ovarian cancers. The effects of the treatment on mRNA and protein levels of human epidermal growth factor (EGF) receptors (EGFR and HER-2) in ovarian tumors were determined by RT-PCR and immunoblotting. In Experiment 1, nude mice bearing ES-2 ovarian tumors were injected i.v. with 250 nmol/kg doses of AN-207, AN-201, the carrier [D-Lys ]LHRH, an unconjugated mixture of AN-201 and [D-Lys ]LHRH or vehicle. AN-207 caused a significant ( <0.01) 59.5% inhibition in tumor growth while its components were ineffective. In Experiment 2, mice with large ES-2 tumors were treated with AN-207 or AN-201 at 250 nmol/kg. Again, AN-207, but not AN-201, inhibited tumor growth. In Experiment 3, the site of action of AN-207 was investigated. The blockade of LHRH receptors with Cetrorelix partially suppressed the antitumor effect of AN-207. Treatment with AN-207 significantly ( <0.01) decreased the expression of mRNA for EGFR, and HER-2 by 27 and 34%, respectively, as compared to controls and reduced the receptor protein levels of EGFR and HER-2 by 35 and 36%, respectively ( <0.05). The results indicate that cytotoxic LHRH analog AN-207 could be considered for chemotherapy of ovarian cancers expressing LHRH receptors.

Animals↗

PubMed2002

No effect of transfusion transmitted virus viremia on the distribution and activation of peripheral lymphocytes in hemodialyzed patients.

AIM: We aimed to examine the distribution and activation of peripheral T cells in TTV positive (n = 32) and negative (n = 17) hemodialyzed patients. The control group (n = 20) consisted of healthy blood donors. METHOD: TTV-DNA was detected by seminested PCR. CD3, CD4, CD8, CD19, CD56, CD3/HLA-DR, CD3/CD69 and the Th1/Th2 ratio of T cells were analyzed by flow cytometry. Circulating IFN-gamma, IL-2, IL-4, IL-6, IL-10, IL-13, TNF-alpha, TGF-beta levels were measured by ELISA in the sera. RESULTS: There was no difference between the CD3, CD4, CD8 and CD19 values of HD subjects. In addition, the expression of both activation markers, HLA-DR and CD69, was significantly elevated in the TTV-positive and -negative HD groups compared to the controls, but not showing any difference from each other. The measurements of intracellular cytokines showed the enhanced occurrence of INF-gamma + CD4 T cells, and decreased appearance of IL-4 + CD4 lymphocytes in the HD groups without any significant difference between the TTV virus positive and negative patients. In addition, HD also elevated the expression of IL-10 in CD4 and CD8 (Th2) cells. There were only two significant changes in the levels of circulating cytokines: (a) IL-2 increased; (b) IL-13 decreased in both groups of HD patients compared to the controls, independently of TTV positivity or negativity. CONCLUSIONS: We assume that transfusion-transmitted virus does not cause any specific change in the distribution and activation of lymphocytes in the peripheral blood of hemodialyzed patients. Hemodialysis itself, however, results in a significant activation of peripheral T cells with the domination of increased production of Th1 type cytokines, IFN-gamma, IL-2, in contrast to the decreased synthesis of Th2 type cytokines, IL-4 and IL-13. Furthermore, the increased expression of IL-10 in the CD4 and CD8 cells of HD patients can be the sign of a contraregulatory Th2 activation as an answer on the Th1 effect.

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PubMed2002

Effective treatment of experimental DU-145 prostate cancers with targeted cytotoxic somatostatin analog AN-238.

We evaluated the effectiveness of targeted cytotoxic analog of somatostatin (SST) AN-238, consisting of 2-pyrrolinodoxorubicin (AN-201) linked covalently to SST octapeptide carrier RC-121 in DU-145 human androgen-independent prostate cancers xenografted into nude mice. We also investigated the expression of mRNAs for SST receptor subtypes 2A and 5 (sst2A and sst5) in DU-145 tumors. After 8 weeks of treatment, AN-238 practically arrested the proliferation of DU-145 cancers. The tumor volume in nude mice that received 4 injections of AN-238 at the dose of 150 nmol/kg was 63.4+/-6.7 mm3, nearly 4 times smaller than that in controls which measured 249.1+/-36.3 mm3 (p<0.001). Treatment with AN-238 lowered tumor weight by 68% (p<0.01) compared with the control group and extended the tumor volume doubling time to 184.1+/-69.4 days, versus 32.1+/-6.6 days in controls (p<0.05). No toxicity-related deaths occurred during treatment with AN-238. Cytotoxic radical AN-201 administered alone or in an unconjugated mixture with carrier RC-121 inhibited the growth of DU-145 tumors only after the third and fourth injection and was toxic. The expression of mRNA for sst2A and sst5 was detected in all specimens of control DU-145 tumors and in tumors treated with AN-238. The present study demonstrates the high efficacy of SST-receptor-targeted chemotherapy in a model of human androgen-independent prostatic carcinoma.

Animals↗

PubMedDate not supplied

Characterizing observation volumes and the role of excitation saturation in one-photon fluorescence fluctuation spectroscopy.

Fluorescence correlation spectroscopy (FCS) and related distribution analysis techniques have become extremely important and widely used research tools for analyzing the dynamics, kinetics, interactions, and mobility of biomolecules. However, it is not widely recognized that photophysical dynamics can dramatically influence the calibration of fluctuation spectroscopy instrumentation. While the basic theories for fluctuation spectroscopy methods are well established, there have not been quantitative models to characterize the photophysical-induced variations observed in measured fluctuation spectroscopy data under varied excitation conditions. We introduce quantitative models to characterize how the fluorescence observation volumes in one-photon confocal microscopy are modified by excitation saturation as well as corresponding models for the effect of the volume changes in FCS. We introduce a simple curve fitting procedure to model the role of saturation in FCS measurements and demonstrate its accuracy in fitting measured correlation curves over a wide range of excitation conditions.

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